OP0146 GENETIC EVIDENCE REVEALS A CAUSAL RELATIONSHIP BETWEEN PHYSICAL ACTIVITY AND OSTEOARTHRITIS
Authors: J. Y. Chen, Q. Feng, Q. Q. Ma, H. Zhang, Y. Feng, X. Yang, Q. Dong, Q. Yu, P. F. He, X. Li, S. X. Zhang
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Osteoarthritis (OA) is a common musculoskeletal disease [1]. Research evidence indicates that exercise can reduce OA patients' joint pain to an extent [2]. However, the genetic causal relationship between physical activity (PA) and OA remains vague. <h3>Objectives</h3> In our study, Mendelian randomization (MR) was conducted to explore the causal assosiation of PA and OA. <h3>Methods</h3> PA was divided into two different phenotypes, including sedentary behavior and physically active behavior. Genome-wide association study (GWAS) data for PA [3] was obtained from the UK Biobank. We selected single nucleotide polymorphisms (SNPs) that were strongly associated (p &lt; 5 × 10−8) with two PA phenotypes and checked them on PhenoScanner removing SNPs associated with confounders. The OA data was derived from a GWAS among 455,221 individuals (77052 samples and 378169 controls) of European descent [4]. To assess the causality of PA on OA, inverse variance weighting (IVW), MR-Egger, and weighted median (WM), were employed. IVW was applied for the principal analysis. To ensure the robustness of our result, Cochran's Q test, MR-Egger intercept test, and leave-one-out analysis were used to assess the sensitivity of the study. <h3>Results</h3> Among the tested sedentary behavior, the length of mobile phone use increases the risk of knee OA (odds ratio (OR):1.560, 95% confidence interval (CI):1.167-2.086, p=2.683×10-3) and hip or knee OA (OR:1.334, 95%CI:1.026-1.734, p=3.141×10-2). After removing SNPs associated with smoking, alcohol consumption, lymphocyte count, and heart disease, we also found evidence of a potential adverse effect of genetically predicted time spent watching television (TV) on knee OA (OR:1.913, CI:1.450-2.523, p=4.388×10-6) and hip or knee OA (OR:1.611, 95%CI:1.288-2.014, p=2.860×10-5). No potential causal link was observed between physically active behavior and OA through the IVW analysis(p&gt;0.05). MR-Egger and WM yielded identical effects to IVW. Any potential heterogeneity or pleiotropy was not found. <h3>Conclusion</h3> Sedentary behavior can increase the risk of OA, but no direct causal relationship is observed between physically active behavior and OA. It indicates that OA patients should avoid a sedentary lifestyle. <h3>References</h3> [1] Martel-Pelletier, J., Barr, A. J., Cicuttini, F. M., Conaghan, P. G., Cooper, C., Goldring, M. B., Goldring, S. R., Jones, G., Teichtahl, A. J., &amp; Pelletier, J. P. (2016). Osteoarthritis. Nature reviews. Disease primers, 2, 16072. https://doi.org/10.1038/nrdp.2016.72 [2] Hinman, R. S., Hall, M., Comensoli, S., &amp; Bennell, K. L. (2023). Exercise &amp; Sports Science Australia (ESSA) updated Position Statement on exercise and physical activity for people with hip/knee osteoarthritis. Journal of science and medicine in sport, 26(1), 37–45. https://doi.org/10.1016/j.jsams.2022.11.003 [3] Klimentidis, Y. C., Raichlen, D. A., Bea, J., Garcia, D. O., Wineinger, N. E., Mandarino, L. J., Alexander, G. E., Chen, Z., &amp; Going, S. B. (2018). Genome-wide association study of habitual physical activity in over 377,000 UK Biobank participants identifies multiple variants including CADM2 and APOE. International journal of obesity (2005), 42(6), 1161–1176. https://doi.org/10.1038/s41366-018-0120-3 [4] Tachmazidou, I., Hatzikotoulas, K., Southam, L., Esparza-Gordillo, … Zeggini, E. (2019). Identification of new therapeutic targets for osteoarthritis through genome-wide analyses of UK Biobank data. Nature genetics, 51(2), 230–236. https://doi.org/10.1038/s41588-018-0327-1 <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.